<i>H19</i> controls reactivation of the imprinted gene network during muscle regeneration

Martinet, Clémence; Monnier, Paul; Louault, Yann; Benard, Matthieu; Gabory, Anne; Dandolo, Luisa

doi:10.1242/dev.131771

Cited by 68 publications

(60 citation statements)

References 50 publications

(72 reference statements)

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“…Thus, HepG2 cells were transfected with control siRNA (siCon) or H19-specific siRNA (siH19) (10), followed by glucose production assays. When H19 was downregulated ( Figure 3A), the expression of Igf2 was not affected ( Figure 3A), despite reports that H19 and Igf2 are coregulated in mouse skeletal muscle (8,18). There was a significant decrease in glucose output in the H19-knockdown cells ( Figure 3B), suggesting a positive role of H19 in glucose production.…”

Section: Resultsmentioning

confidence: 82%

“…To further characterize H19's role in HGP and glucose metabolism, we used a whole-body H19-KO mouse model (17,18). The KO mice showed an overgrowth phenotype and skeletal muscle hyperplasia and hypertrophy (17,18), consistent with the role of the imprinted H19-Igf2 locus in embryo development and growth regulation (8). However, the metabolic phenotype of the KO mice has not been previously documented.…”

Section: Resultsmentioning

confidence: 99%

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Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia

et al. 2018

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Excessive hepatic glucose production (HGP) contributes significantly to the hyperglycemia of type 2 diabetes; however, the molecular mechanism underlying this dysregulation remains poorly understood. Here, we show that fasting temporally increases the expression of H19 long noncoding RNA (lncRNA) in nondiabetic mouse liver, whereas its level is chronically elevated in diet-induced diabetic mice, consistent with the previously reported chronic hepatic H19 increase in diabetic patients. Importantly, liver-specific H19 overexpression promotes HGP, hyperglycemia, and insulin resistance, while H19 depletion enhances insulin-dependent suppression of HGP. Using genome-wide methylation and transcriptome analyses, we demonstrate that H19 knockdown in hepatic cells alters promoter methylation and expression of Hnf4a, a master gluconeogenic transcription factor, and that this regulation is recapitulated in vivo. Our findings offer a mechanistic explanation of lncRNA H19's role in the pathogenesis of diabetic hyperglycemia and suggest that targeting hepatic H19 may hold the potential of new treatment for this disease.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia

et al. 2018

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“…The significance of this upregulation is currently unclear. Since H19 was shown to play an important role in adult stem cell maintenance (71,72) and also activates Wnt signaling by upregulation of β -catenin (73), it is possible that this H19 upregulation may be associated with the observed MSC-like phenotype of MNCs. Intriguingly, there is a subset of miRNAs that are perfectly anti-correlated to the expression of their primary lncRNA.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity

et al. 2016

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Myoblasts are precursor skeletal muscle cells that differentiate into fused, multinucleated myotubes. Current single-cell microfluidic methods are not optimized for capturing very large, multinucleated cells such as myotubes. To circumvent the problem, we performed single-nucleus transcriptome analysis. Using immortalized human myoblasts, we performed RNA-seq analysis of single cells (scRNA-seq) and single nuclei (snRNA-seq) and found them comparable, with a distinct enrichment for long non-coding RNAs (lncRNAs) in snRNA-seq. We then compared snRNA-seq of myoblasts before and after differentiation. We observed the presence of mononucleated cells (MNCs) that remained unfused and analyzed separately from multi-nucleated myotubes. We found that while the transcriptome profiles of myoblast and myotube nuclei are relatively homogeneous, MNC nuclei exhibited significant heterogeneity, with the majority of them adopting a distinct mesenchymal state. Primary transcripts for microRNAs (miRNAs) that participate in skeletal muscle differentiation were among the most differentially expressed lncRNAs, which we validated using NanoString. Our study demonstrates that snRNA-seq provides reliable transcriptome quantification for cells that are otherwise not amenable to current single-cell platforms. Our results further indicate that snRNA-seq has unique advantage in capturing nucleus-enriched lncRNAs and miRNA precursors that are useful in mapping and monitoring differential miRNA expression during cellular differentiation.

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“…H19 was the most abundant in both muscles, and its higher levels were found in the soleus. The H19 target genes were regulators of the imprinted gene network of adult skeletal muscles (34). Most of the H19 target genes were not DE between soleus and the quadriceps.…”

Section: Expression Of Muscle-specific Mirs and Lncrna Correlate Withmentioning

confidence: 93%

The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs

et al. 2018

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Adult muscles have a vast adaptation capacity, enabling function switches in response to altered conditions. During intensive physical activity, disease, or aging, adult skeletal muscles change and adjust their functions. The competence to adjust varies among muscles. Muscle-specific molecular mechanisms in healthy and normal conditions could designate changes in physiologic and pathologic conditions. We generated deep mRNA-sequencing data in adult fast and slow mouse muscles, and applying paired analysis, we identified that the muscle-specific signatures are composed of half of the muscle transcriptome. The fast muscles showed a more compact gene network that is concordant with homogenous myofiber typing, compared with the pattern in the slow muscle. The muscle-specific mRNA landscape did not correlate with alternative spicing, alternative polyadenylation, or the expression of muscle transcription factor gene networks. However, we found significant correlation between the differentially expressed noncoding RNAs, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) and their target genes. More than 25% of the genes expressed in a muscle-specific fashion were found to be targets of muscle-specific miRNAs and lncRNAs. We suggest that muscle-specific miRNAs and lncRNAs contribute to the establishment of muscle-specific transcriptomes in adult muscles.-Raz, V., Riaz, M., Tatum, Z., Kielbasa, S. M., 't Hoen, P. A. C. The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs.

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H19 controls reactivation of the imprinted gene network during muscle regeneration

Cited by 68 publications

References 50 publications

Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia

Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia

Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity

The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs

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